The monitoring of therapeutic drug levels and other analytes in biological fluids such as serum, plasma, whole blood, urine and the like has become very useful to provide physicians with information to aid in proper patient management. For example, adjustment of patient dosage, achievement of optimal therapeutic effects, and avoiding useless subtherapeutic or harmful toxic dosage levels can be provided. Conventional techniques which are employed to monitor drug levels or detect other analytes are known and include radioimmunoassays and nonisotopic assays such as fluorescence polarization immunoassays. However, such techniques produce inconsistencies in results because of, for example, variations in the protein concentration of individual patient test samples and the tendency of analytes to bind to such proteins, to thereby prevent the accurate determination thereof.
Although various precipitation reagents have been described to remove or extract such interfering proteins from a test sample, such reagents suffer from a number of disadvantages, particularly for the determination of hydrophobic analytes. For example, U.S. Pat. No. 4,734,378 describes the use of 5-sulfosalicylic acid for extracting digoxin and precipitating protein from a biological test sample, and the use of zinc salts as preciptitation reagents have also been described. However, such precipitation reagents do not maintain hydrophobic analytes in solution and, furthermore, 5-sulfosalicylic acid does not remove hemoglobin from, for example, a whole blood test sample. Moreover, precipitation reagents which have been previously described typically denature and thereby result in significant loss of the binding activity of, for example, antibodies employed in an immunoassay system.